Neuroendocrine Cancer
Conditions
Keywords
neuroendocrine malignancies, pancreatic neuroendocrine tumors (PNETs), gastrointestinal (GI) carcinoids, carfilzomib, Kyprolis, proteasome inhibitors
Brief summary
The purpose of this study is to determine if carfilzomib is safe and effective in the treatment of patients with advanced neuroendocrine tumors.
Detailed description
Neuroendocrine malignancies such as pancreatic neuroendocrine tumors (PNETs) and gastrointestinal (GI) carcinoids, are generally rare but their incidences are increasing. In vitro and in vivo studies have shown that proteasome inhibitors have activity against a variety of tumor types. Carfilzomib (Kyprolis®) is an irreversible proteasome inhibitor with a favorable safety profile that has been studied in a variety of hematologic and solid tumors. Carfilzomib received accelerated approval from the U.S. FDA in 2012, based on a favorable response rate, for the treatment of patients with multiple myeloma who received at least two prior therapies, and demonstrated disease progression within 60 days of completing the last therapy. In this multi-center study, the investigators propose to evaluate carfilzomib for the treatment of patients with advanced neuroendocrine cancers.
Interventions
DRUGCarfilzomib
Sponsors
Amgen
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults with biopsy-proven advanced, unresectable or metastatic, well-to-moderately differentiated (or low grade) neuroendocrine carcinoma, including typical carcinoid, pancreatic islet cell and other well-to-moderately differentiated neuroendocrine carcinomas. 2. Measurable disease per Response Evaluation Criteria in Solid Tumors RECIST v 1.1 criteria. 3. Patients currently receiving or previously treated with single agent sandostatin LAR® are eligible. However, this is not a mandatory criterion to be included in the study. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 5. Adequate hematologic, renal, and hepatic function. 6. Predicted life expectancy \> 12 weeks.
Exclusion criteria
1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, globlet cell carcinoid, atypical carcinoid, anaplastic carcinoid, pulmonary neuroendocrine and small cell carcinoma are not eligible. 2. Patients who had radiation therapy, hormonal therapy, biologic therapy, investigational agents, or chemotherapy for cancer within 21 days or 5 half-lives of any chemotherapy or biologic/targeted agent, whichever is longer, prior to first treatment day of the study. 3. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would impair the ability of the patient to receive protocol treatment. 4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 5. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. 6. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years | Percentage of participants with confirmed complete response (CR) or partial response (PR) (i.e. 2 CRs or PRs at least 4 weeks apart) to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) CR=disappearance of all target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years | Percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) (≥ 6 cycles) according to RECIST v1.1 criteria. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started. |
| Progression Free Survival (PFS) | up to 4 years | Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on the study. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions. Patients who did not have disease progression or death documented were censored on the date of the last visit with adequate assessment. |
| Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | From the day of the first dose to 30 days after the last dose of study medication, up to 4 years | The number of treatment-emergent adverse events will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carfilzomib Carfilzomib - administered as an intravenous (IV) infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.
Cycle 1: First two doses of Carfilzomib 20 mg/m\^2 IV; subsequent doses at 56 mg/m2 IV
Cycle 2 onwards: Carfilzomib 56 mg/m\^2 IV | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Death | 2 |
| Overall Study | Progressive Disease | 37 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Carfilzomib |
|---|---|
| Age, Continuous | 63 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Region of Enrollment United States | 62 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 62 |
| other Total, other adverse events | 61 / 62 |
| serious Total, serious adverse events | 31 / 62 |
Outcome results
Primary
Overall Response Rate (ORR)
Percentage of participants with confirmed complete response (CR) or partial response (PR) (i.e. 2 CRs or PRs at least 4 weeks apart) to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) CR=disappearance of all target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
Population: All enrolled patients who received at least one full or partial dose of the study drug and who had measurable disease at baseline were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carfilzomib | Overall Response Rate (ORR) | 3.226 percentage of participants |
Secondary
Disease Control Rate (DCR)
Percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) (≥ 6 cycles) according to RECIST v1.1 criteria. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started.
Time frame: every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
Population: All enrolled patients who received at least one full or partial dose of the study drug and who had measurable disease at baseline were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carfilzomib | Disease Control Rate (DCR) | 58 percentage of participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
The number of treatment-emergent adverse events will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
Time frame: From the day of the first dose to 30 days after the last dose of study medication, up to 4 years
Population: All enrolled patients who received at least one full or partial dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carfilzomib | Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability | 56 Participants |
Secondary
Progression Free Survival (PFS)
Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on the study. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions. Patients who did not have disease progression or death documented were censored on the date of the last visit with adequate assessment.
Time frame: up to 4 years
Population: All enrolled patients who received at least one full or partial dose of the study drug and who had measurable disease at baseline were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carfilzomib | Progression Free Survival (PFS) | 8 months |